Endometriosis is a common gynecologic disease involving endometrial tissue located outside of the uterine cavity. It causes debilitating pain and frustrating infertility in women with this disease. Despite extensive nvestigation, no study has shown a specific gene involved in endometriosis, but a genetic predisposition is likely. To define the molecular profile of women with endometriosis, we have recruited 84 endometriosis cases in the Houston area and 47 control patients. Genomic DMA is being analyzed by comparative genomic hybridization using the Agilent platform, mRNA levels are analyzed with Illumina microarrays, and microRNAs by the Illumina/Solexa sequencing platform. The overall hypothesis for this project is that regulatory defects in microRNAs play a central early role in organizing the molecular changes involved in endometriosis and, in doing so, determine important aspects of its clinical behavior and response to therapy. The specific aims of the project involve identifying microRNA regions in genomic DNA associated with endometriosis, profiling microRNA signatures of normal endometrium and endometriotic tissues, validating microRNA:mRNA targets, and creating in vitro models for studying the role of candidate microRNAs in uterine function and dysfunction. Our proposed research will allow us to develop cost-effective, highthroughput strategies for classifying individual patients with endometriosis at a molecular (microRNA, mRNA, and genomic) level with the long-term goal of developing patient-specific treatment protocols.